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Ultrasound neuromodulation of cultured hippocampal neurons

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Abstract

Ultrasound is becoming an emerging and promising method for neuromodulation due to its advantage of noninvasiveness and its high spatial resolution. However, the underlying principles of ultrasound neuromodulation have not yet been elucidated. We have herein developed a new in vitro setup to study the ultrasonic neuromodulation, and examined various parameters of ultrasound to verify the effective conditions to evoke the neural activity. Neurons were stimulated with 0.5 MHz center frequency ultrasound, and the action potentials were recorded from rat hippocampal neural cells cultured on microelectrode arrays. As the intensity of ultrasound increased, the neuronal activity also increased. There was a notable and significant increase in both the spike rate and the number of bursts at 50% duty cycle, 1 kHz pulse repetition frequency, and the acoustic intensities of 7.6 W/cm2 and 3.8 W/cm2 in terms of spatial-peak pulse-average intensity and spatial-peak temporal-average intensity, respectively. In addition, the impact of ultrasonic neuromodulation was assessed in the presence of a gamma-aminobutyric acid A (GABAA) receptor antagonist to exclude the effect of activated inhibitory neurons. Interestingly, it is noteworthy that the predominant neuromodulatory effects of ultrasound disappeared when the GABAA blocker was introduced, suggesting the potential of ultrasonic stimulation specifically targeting inhibitory neurons. The experimental setup proposed herein could serve as a useful tool for the clarification of the mechanisms underlying the electrophysiological effects of ultrasound.

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Acknowledgements

We thank Prof. Tae-Seong Kim from Department of Biomedical Engineering, College of Electronics and Information, Kyung Hee University for offering ultrasound transducer and helpful comments during the writing of the manuscript. This research was supported by the National Research Foundation of Korea (NRF-2019M3C1B8090805, NRF-2022R1I1A4063209) and by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (1711139110, KMDF_PR_20210527_0006).

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Authors and Affiliations

  1. Department of Electronic and Electrical Engineering, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea

    Seoyoung Hwang & Sang Beom Jun

  2. Graduate Program in Smart Factory, Ewha Womans University, Seoul, Republic of Korea

    Sang Beom Jun

  3. Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Republic of Korea

    Sang Beom Jun

  4. Seoul National University Hospital Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

    Seoyoung Hwang

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  1. Seoyoung Hwang
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Contributions

Conceptualization: all authors. Methodology: HS. Investigation: HS. Writing—original draft preparation: HS. Writing—review and editing: All authors. Approval of final manuscript: all authors.

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Correspondence to Sang Beom Jun.

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The authors have no conflicts of interest to disclose.

Ethical approval

The procedures followed and the care of the animals were approved by the Institutional Animal Care and Use Committee in Ewha Womans University (Approval no. 17-010).

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Hwang, S., Jun, S.B. Ultrasound neuromodulation of cultured hippocampal neurons. Biomed. Eng. Lett. 14, 79–89 (2024). https://doi.org/10.1007/s13534-023-00314-7

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